Cortical cholinergic function and deficits in visual attentional performance in rats following 192 IgG-saporin-induced lesions of the medial prefrontal cortex
Cortical cholinergic function and deficits in visual attentional performance in rats following 192 IgG-saporin-induced lesions of the medial prefrontal cortex
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DOI：
10.1093/cercor/bhh052
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发表时间：
2004-08-01
期刊：
影响因子：
3.7
通讯作者：
Robbins, TW
中科院分区：
文献类型：
--
作者：
Dalley, JW;Theobald, DE;Robbins, TW
基底前脑(BF)皮质胆碱能系统的损伤损害了啮齿动物在五种选择视觉注意任务中的表现。这项研究考察了使用192种胆碱能免疫毒素-Saporin选择性消耗前额叶皮质(PFC)中乙酰胆碱的效果。大鼠接受了检测短暂视觉刺激的训练，这些刺激要么在时间和空间上都不可预测地出现，以增加注意力负荷，要么在要求较低的条件下，刺激在时间和空间上是可预测的。训练结束后，将192个免疫球蛋白皂苷(50 ng或100 ng/次)或其载体注入双侧前额叶腹内侧。100 ng损伤组在术后表现出暂时性的持续性增加，特别是当视觉刺激在时间上不可预测的时候。在注意力负荷增强的情况下，两组损伤组的警觉性降低，以及持续性反应的恢复，特别是在许多试验中持续的高靶点频率下。患中风的受试者也更容易冲动，预测错误增加。全身注射M受体拮抗剂东莨菪碱后，100 ng组的注意正确率较假手术组进一步降低。这些发现与BF胆碱能神经元对PFC功能的重要调制影响是一致的，特别是在注意需求增加的情况下。
Lesions of the basal forebrain (BF) cortical cholinergic system impair performance on a rodent five-choice visual attentional task. This study examines the effects on the same task of selective depletion of acetylcholine from the prefrontal cortex (PFC) using 192 IgG-saporin, the cholinergic immunotoxin. Rats were trained to detect brief visual stimuli, either presented unpredictably both temporally and spatially to increase attentional load, or under less demanding conditions where stimuli were temporally and spatially predictable. Following training, 192 IgG-saporin (50 ng or 100 ng/infusion) or its vehicle was infused bilaterally into the ventromedial PFC. The 100 ng lesion group exhibited post-operatively a transient increase in perseveration, specifically when the visual stimuli were temporally unpredictable. A vigilance decrement, as well as a reinstatement of perseverative responding occurred in both lesion groups under conditions of enhanced attentional load, specifically with high target frequency sustained over many trials. Lesioned subjects were also more impulsive with increased anticipatory errors. Systemic administration of the muscarinic receptor antagonist scopolamine further dissociated the groups with attentional accuracy in the 100 ng group decreasing relative to shams. These findings are consistent with an important modulatory influence of PFC function by BF cholinergic neurons, particularly during increased attentional demand.